Health-related quality of life at 3 months following head and neck cancer treatment is a key predictor of longer-term outcome and of benefit from using the patient concerns inventory.

INTRODUCTION: During clinical follow-up it can be difficult to identify those head and neck cancer (HNC) patients who are coping poorly and could benefit from additional support. Health-related quality of life (HRQOL) questionnaires and prompt lists provide a means by which patients can express their perceived outcomes and raise concerns. The first aim of this secondary analysis following a randomized trial was to explore which patient characteristics, at around 3 months following treatment completion (baseline), best predict HRQOL 12 months later. The second aim was to attempt to ascertain which patients were most likely to benefit from using prompt list. METHODS: Cluster-controlled pragmatic trial data were analyzed. HRQOL was measured by the University of Washington Quality of life questionnaire (UW-QOLv4). The prompt list was the Patient Concerns Inventory (PCI-HN). RESULTS: The trial involved 15 eligible consultants and a median (inter-quartile range) of 16 (13-26) primary HNC patients per consultant, with 140 PCI patients and 148 controls. Baseline HRQOL was the dominant predictor of 12-month HRQOL with other predictors related to social, financial, and lifestyle characteristics as well as clinical stage and treatment. Although formal statistical tests for interaction were non-significant the trend in analyses over a range of outcomes suggested that patients with worse baseline HRQOL could benefit more from the PCI-HN. DISCUSSION: HRQOL early post-treatment is a key predictor of longer-term outcome. Measuring and using HRQOL and the PCI-HN are not only surrogates for predicting HRQOL at 15 months post-treatment, but also tools to help guide interventions.

Balancing patients' fears of recurrence and fears of COVID-19 when considering their preference for review consultations.

PURPOSE: Head and neck cancer (HNC) patients may experience fears regarding cancer recurrence (FoR) and of catching COVID-19. There could be unease for attending hospital clinics for face to face (F2F) examination. F2F benefit in cancer surveillance has to be balanced against the risk of virus transmission. This study aimed to report perceptions of fear of cancer and fear of COVID-19 and to report patient preference for follow-up consultation in HNC survivors during the COVID-19 pandemic. METHODS: The study ran from lockdown in England on 24th March to 29th July 2020. Patients were offered preference to postpone their consultation, to have it by telephone, or F2F. A postal survey was undertaken in the 2 weeks post-consultation (actual or postponed). RESULTS: There were 103 patients. Initial action by consultant and patient resulted in 51 postponed consultations, 35 telephone consultations and 17 F2F meetings, with 10 F2F triggered by the patient. There were 58 responders to the survey and most (39) had a clear preference for one mode of follow-up consultation during the COVID-19 pandemic, with half (19) preferring F2F. A similar response was seen regarding their consultations in general to address unmet needs and concerns, with 38 having a preferred mode, 29 preferring F2F. Serious fears about recurrence and COVID-19 were at relatively low levels with a tendency to be more concerned about recurrence. CONCLUSION: Any redesign of mode and frequency of out-patient follow-up in light of COVID-19 should be undertaken in discussion with patient groups and with individual patients.

First Results from Moderna’s Coronavirus Vaccine

This morning brought news from Moderna of the very first human results from trials of their closely-watched mRNA vaccine candidate (mRNA-1273) against the coronavirus. Here’s Stat on the news, and here’s Endpts – the results can be summed up pretty quickly, because it’s all just at the press-release level to start with. The trial was dosing volunteers in Phase I at three levels 25 micrograms, 100 micrograms, and 250 micrograms of the mRNA species. First off, immunogenicity (whether or not these doses caused people to produce antibodies). The good news there is that every participant at every dose level began producing antibodies (in other words, they “seroconverted) by day 15 after the first injection. The actual amount of antibodies produced went up in the higher-dosage group, and for the 25 and 100 µg folks, it went up after the second “booster” shot of mRNA as well. (The high-dose 250 µg voluteers seem to have maxed out after the first shot, actually).

Criticism of the Oxford Coronavirus Vaccine

This piece at Forbes by Bill Haseltine has set off a lot of comment – it’s a look at the Oxford group’s vaccine candidate as compared to the SinoVac candidate, and you may recall (background here) that these are the two teams that have separately reported that their vaccines appear to protect rhesus monkeys from infection after exposure to the coronavirus. Haseltine has some criticisms of the Oxford data, and as you will see from that link to his name, his opinions deserve to be taken seriously. So what’s going on? Update: here’s the take on this at BioCentury. Looking at the preprint on the Oxford results, Haseltine has a problem with the claim that the monkeys were protected from infection by a dose of ChAdOx1 nCoV-19. The key data are in the preprint’s Figure 3. The Oxford team checked for viral RNA several different ways. One was using bronchoaveolar lavage (BAL fluid), a sampling technique that involves running a bronchoscope down into the lungs and washing out aveolar spaces – a pretty darn invasive assay, which is why you don’t hear about it all that much compared to the still-not-so-nonivasive nose swabs. BAL fluid of the virus-exposed unvaccinated animals showed coronavirus genomic RNA throughout the study, and viral subgenomic RNA (more indicative of active replication) at days 3 and 5 after exposure. Meanwhile, the vaccinated animals showed the genomic RNA in only two monkeys, and no subgenomic RNA at all.

Another Set of Coronavirus Vaccine Candidates

I surveyed the coronavirus vaccine landscape in this post, and then detailed some of the larger efforts in the field here (several updates have been added to that one since its initial posting). Now it’s time to look at several programs that aren’t in either of those, but still have plenty of serious science behind them. For an example of a relatively new technology that’s now in use for human patients, there’s the VSV (vesicular stomatitis virus) platform, which was used to produce the Ebola vaccine now manufactured by Merck. Stat has an excellent long-form article from earlier this year about how this came about, and it’s well worth a read, both for the history itself and as a look into the ups and downs of vaccine research in general. The Yale team behind that one had developed a promising vaccine candidate for the SARS coronavirus during its epidemic, and they’re using those lessons in their current work. If you look at that second link above on vaccine candidates, you will note that there are several using adenovirus vectors – this is conceptually the same sort of thing, but using a livestock virus (VSV) instead of human or primate-associated adenoviruses. I don’t know if the Yale team has partnered with anyone yet, but I should also mention another connection of theirs, a spinoff company called CaroGen that has another engineered virus platform that is also being put to use against SARS-CoV-2. These projects are aiming at FDA approval for Phase I trials, but there’s no word yet on what such an application might go in.

Monoclonal Antibodies and Vaccines: Q and A

The second reason is even more salient: the great majority of people who have recovered during the COVID-19 pandemic did so because they raised their own neutralizing antibodies to the virus. ... There is, for example, a canine coronavirus vaccine available, although one has to note immediately that it’s for an enteric virus, not a respiratory one, and that it itself is of no use whatsoever (in dogs or in people) against the COVID-19 epidemic.

What’s Up With Ivermectin?

One of the small-molecule drugs that’s getting attention as a possible coronavirus treatment is Ivermectin, which is an interesting story from a couple of different directions. I’ve been getting some inquiries about it, so I thought it was time to have a look. Ivermectin and COVID-19: So what is this compound doing in the news with the coronavirus? Its ion-channel mechanism of action against parasites has no application to viruses. But it has been shown several times to have activity in cell assays against Dengue infection and to reduce viral loads in the mosquito vectors (see this paper and references therein), although the reasons for this are still unknown. There have been some human studies for efficacy, but all I can find out is that a preliminary read showed no reduction of viral load in the infected patients, and there seems to have been no update. But since denguevirus is also a single-strand positive-sense RNA virus, Ivermectin has come up as a possible coronavirus drug, mechanism or not.

Mutations in the Coronavirus Spike Protein

The last post talked about antibodies to the spike protein of the coronavirus, and one of the main things that everyone has to keep an eye on are the mutations in that area. That has implications for monoclonal antibody therapy, for vaccine production, and for the behavior of the coronavirus itself. Antibodies against the Spike protein could range from neutralizing ones that will stop the virus in its tracks all the way to others that would cause antibody-dependent enhancement and make the viral infection even worse (see below), and we don’t know how the mutational landscape might alter the activity of any given monoclonal candidate. A new preprint on spike muations (from researchers at Los Alamos, Duke, and Sheffield) has gotten a great deal of attention in the last couple of days, and I think that a detailed look at it would be useful to help explain these issues.

Get Real

Since this is going to be a post about the coronavirus, let’s start off with this PSA: wash your hands. ... OK, either tomorrow or Friday I hope to do a post on all the things that are going on in the biopharma industry for a possible coronavirus treatment. ... It was clearly related to the virus from the first case (reported on January 19 in the same county in Washington state), descended from it in a way that makes it almost certain that the coronavirus has been spreading undetected among that population for weeks.

Antiviral Theatrics?

This, though, is an official organ of the Chinese state – none more so – showing all sorts of white-fog-spraying devices being deployed outdoors, with the caption “Full-front disinfection work has started in #Wuhan, an effort to contain the spread of #coronavirus“. ... Maybe there’s something in the mix that someone thinks will do some good against coronavirus particles – I doubt if they’re correct, if so – or maybe the whole thing is just meant to show that the Authorities Are Doing Something.

Details of a New Anti-Coronovirus Neutralizing Antibody

There’s a lot of work being done on antibodies for the coronavirus and on the protein domains they recognize. This of course has bearing both on the idea of monoclonal antibody therapies and for the vaccines that are in development, so let’s have a look at the new data. For reference, here’s a background post on some of the proteins that the virus makes and the mutations that have been spotted in them, here’s my post on the basics of antibodies and immunology as relating to the epidemic, with an update here, and here’s my earlier post on monoclonal antibodies as a treatment, now updated with some new items.

Monoclonal Antibodies for the Coronavirus

Antibodies as a therapy Let’s have a look at what is (in my opinion) probably our best shot at a reasonably short-term targeted therapy against the COVID-19 epidemic: the possibility of using monoclonal antibodies.